Hedgehog is involved in prostate basal cell hyperplasia formation and its progressing towards tumorigenesis

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Abstract

The role of Hedgehog signaling in human basal cell hyperplasia formation and its progressing towards tumorigenesis was investigated. Hedgehog signaling members including PTCH1, GLI1, GLI2, and GLI3 were found co-localized with p63 expression in most hyperplastic basal cells, but rarely in normal basal cells, suggesting Hedgehog involvement in basal cell hyperplasia formation. Both CK-14 and CK-8 markers were found co-localized in the majority of hyperplastic basal cells, but relatively few in the normal basal cells, indicating a Hedgehog-promoted transitory differentiation. Furthermore, CK-14 and PTCH1 were found co-localized with CD44 in the hyerplastic basal cells, in a way similar to the CD44 co-localization with PTCH1 and GLI1 in the cancer cells. Together, the present study indicated Hedgehog involvement in forming basal cell hyperplasia and its progressing towards cancer, presumably by transforming the normal basal stem cells into the cancer stem cells where persistent Hedgehog activation might be mandatory for tumorigenesis.

Section snippets

Materials and methods

Human tissues. The human prostate tissues were obtained from 42 patients who had received radical prostectomy at Department of Pathology, Chung Shan Medical University, Taichung, Taiwan, or Department of Urology, Changhua Christian Hospital, Changhua, Taiwan. The presence of normal basal cell layer (NBCL), basal cell hyperplasia (BCH), and prostate cancer (CaP) was confirmed by clinical pathologists. Tissue donors were informed with written consents before obtainment of their prostate

Dynamic p63 expression during transformation of normal basal cell layer towards hyperplasia and cancer

Taking advantage of the heterogeneity of human prostate tumors, we examined the dynamic changes of p63 expression during the transformation of NBCL to BCH and further towards CaP. Because p63 had been widely used as a basal cell marker, we used p63 to define BCH, irrespective of whether the specimen had been diagnosed as CaP or non-CaP. As such, BCH was used instead of the generally used benign prostatic hyperplasia (BPH). In the normal prostate sites, p63 expression was detected in the slim

Acknowledgments

This study was supported by grants from Department of Heath (DOH 95-TD-B-111-TM009), Taiwan to D.P.C.L. and from National Science Council (NSC 95-2320-B-040-035), Taiwan to H.H.C.

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